Nocistatin and nociceptin exert opposite effects on the excitability of central amygdala nucleus-periaqueductal gray projection neurons.
Central amygdala nucleus (CeA)-periaqueductal gray (PAG) pathway is the component of descending antinociceptive circuitry. Nociceptin/orphanin FQ (N/OFQ) and nocistatin (NST) produce supraspinal pronociceptive and antinociceptive effects, respectively. We hypothesized that opposite effects of N/OFQ and NST on supraspinal pain modulation result from their opposing effects on the excitability of CeA-PAG projection neurons. This hypothesis was tested by investigating electrophysiological effects of N/OFQ and NST on medial CeA neurons that project to PAG (CeA(M)-PAG). N/OFQ hyperpolarized CeA(M)-PAG projection neurons by enhancing inwardly rectifying potassium conductance. In contrast, NST depolarized CeA(M)-PAG neurons by causing the opening of TRPC cation channels via G(alphaq/11)-PLC-PKC pathway. CeA(M)-PAG neurons hyperpolarized by N/OFQ express CRF or neurotensin mRNA. NST-responsive CeA(M)-PAG neurons contain CRF or substance P mRNA. Our study provides the evidence that the molecular and cellular basis for opposite effects of N/OFQ and NST on supraspinal pain regulation is their opposing effects on the excitability of peptidergic CeA(M)-PAG neurons.
Chen
Ying-Ling
YL
Department of Physiology, Chang Gung University School of Medicine, Kwei-San, Tao-Yuan, Taiwan, ROC.
Li
Allen H
AH
Yeh
Tu-Hsueh
TH
Chou
An-Hsun
AH
Wang
Hung-Li
HL
D000679:Amygdala / Q000033:anatomy & histology / Q000378:metabolism*; D000818:Animals; D004525:Efferent Pathways / Q000033:anatomy & histology / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D018847:Opioid Peptides / Q000378:metabolism*; D010146:Pain / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010487:Periaqueductal Gray / Q000033:anatomy & histology / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000097629:Nociceptin
D018847:Opioid Peptides; D024661:Potassium Channels, Inwardly Rectifying; D000097629:Nociceptin; C111148:nocistatin